CN100398521C - 作为金属蛋白酶mmp12抑制剂的2,5-二氧代咪唑烷-4-基乙酰胺及类似物 - Google Patents
作为金属蛋白酶mmp12抑制剂的2,5-二氧代咪唑烷-4-基乙酰胺及类似物 Download PDFInfo
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- CN100398521C CN100398521C CNB038237970A CN03823797A CN100398521C CN 100398521 C CN100398521 C CN 100398521C CN B038237970 A CNB038237970 A CN B038237970A CN 03823797 A CN03823797 A CN 03823797A CN 100398521 C CN100398521 C CN 100398521C
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- Prior art keywords
- acetamide
- dioxoimidazolidin
- ethyl
- methyl
- phenyl
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- 101000577881 Homo sapiens Macrophage metalloelastase Proteins 0.000 title claims abstract description 4
- 239000003112 inhibitor Substances 0.000 title abstract description 11
- HCHODUQYFOQMJB-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)acetamide Chemical class NC(=O)CC1NC(=O)NC1=O HCHODUQYFOQMJB-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 76
- 238000000034 method Methods 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 7
- 208000006673 asthma Diseases 0.000 claims abstract description 5
- 230000000414 obstructive effect Effects 0.000 claims abstract description 4
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 4
- -1 2,3-dihydrobenzofuryl Chemical group 0.000 claims description 102
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 98
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 86
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 68
- 229910052760 oxygen Inorganic materials 0.000 claims description 67
- 239000001301 oxygen Substances 0.000 claims description 61
- 125000004122 cyclic group Chemical group 0.000 claims description 55
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 53
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
- 229910052736 halogen Inorganic materials 0.000 claims description 36
- 150000002367 halogens Chemical class 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 229920006395 saturated elastomer Polymers 0.000 claims description 27
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 17
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000001544 thienyl group Chemical group 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 5
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- CYUXVILHVJSGAL-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(4-fluorophenyl)phenyl]ethyl]acetamide Chemical compound C1=CC(F)=CC=C1C(C=C1)=CC=C1CCNC(=O)CC1C(=O)NC(=O)N1 CYUXVILHVJSGAL-UHFFFAOYSA-N 0.000 claims description 2
- 102100027998 Macrophage metalloelastase Human genes 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims 3
- 125000003386 piperidinyl group Chemical group 0.000 claims 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 3
- ZTNOJMSNUNOJPU-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(3-methoxyphenyl)phenyl]ethyl]acetamide Chemical compound COC1=CC=CC(C=2C=CC(CCNC(=O)CC3C(NC(=O)N3)=O)=CC=2)=C1 ZTNOJMSNUNOJPU-UHFFFAOYSA-N 0.000 claims 2
- 150000002431 hydrogen Chemical group 0.000 claims 2
- 239000011593 sulfur Substances 0.000 claims 2
- SIEGPBNPMLNAIX-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-(1-hydroxy-1-phenylpropan-2-yl)acetamide Chemical compound C=1C=CC=CC=1C(O)C(C)NC(=O)CC1NC(=O)NC1=O SIEGPBNPMLNAIX-UHFFFAOYSA-N 0.000 claims 1
- VWFHRFVESALJFX-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-(2-phenylcyclopropyl)acetamide Chemical compound C1C(C=2C=CC=CC=2)C1NC(=O)CC1NC(=O)NC1=O VWFHRFVESALJFX-UHFFFAOYSA-N 0.000 claims 1
- SFINQEGITZLZLM-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-(2-thiophen-2-ylethyl)acetamide Chemical compound C=1C=CSC=1CCNC(=O)CC1NC(=O)NC1=O SFINQEGITZLZLM-UHFFFAOYSA-N 0.000 claims 1
- XIWREPKZTFSDQK-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-(4-fluorophenyl)ethyl]acetamide Chemical compound C1=CC(F)=CC=C1CCNC(=O)CC1C(=O)NC(=O)N1 XIWREPKZTFSDQK-UHFFFAOYSA-N 0.000 claims 1
- SYOCAUUAJRQWET-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-(4-naphthalen-2-ylphenyl)ethyl]acetamide Chemical compound C=1C=C(C=2C=C3C=CC=CC3=CC=2)C=CC=1CCNC(=O)CC1NC(=O)NC1=O SYOCAUUAJRQWET-UHFFFAOYSA-N 0.000 claims 1
- QOUUSQCTLZIPHV-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-(4-phenoxyphenyl)ethyl]acetamide Chemical compound C=1C=C(OC=2C=CC=CC=2)C=CC=1CCNC(=O)CC1NC(=O)NC1=O QOUUSQCTLZIPHV-UHFFFAOYSA-N 0.000 claims 1
- LUHKICOBAZWLCE-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-(4-phenylphenyl)ethyl]acetamide Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CCNC(=O)CC1NC(=O)NC1=O LUHKICOBAZWLCE-UHFFFAOYSA-N 0.000 claims 1
- KJDLMPRNRVVGBT-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-(4-pyridin-3-ylphenyl)ethyl]acetamide Chemical compound C=1C=C(C=2C=NC=CC=2)C=CC=1CCNC(=O)CC1NC(=O)NC1=O KJDLMPRNRVVGBT-UHFFFAOYSA-N 0.000 claims 1
- QXYKUMMYJROWDF-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-(4-quinolin-3-ylphenyl)propyl]acetamide Chemical compound C=1C=C(C=2C=C3C=CC=CC3=NC=2)C=CC=1C(C)CNC(=O)CC1NC(=O)NC1=O QXYKUMMYJROWDF-UHFFFAOYSA-N 0.000 claims 1
- VCBWZGWLIVTVCF-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-(4-thiophen-2-ylphenyl)ethyl]acetamide Chemical compound C=1C=C(C=2SC=CC=2)C=CC=1CCNC(=O)CC1NC(=O)NC1=O VCBWZGWLIVTVCF-UHFFFAOYSA-N 0.000 claims 1
- ZRWDMKWLUPDQAX-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-(4-thiophen-3-ylphenyl)ethyl]acetamide Chemical compound C=1C=C(C2=CSC=C2)C=CC=1CCNC(=O)CC1NC(=O)NC1=O ZRWDMKWLUPDQAX-UHFFFAOYSA-N 0.000 claims 1
- SMLVTOYIPFGBCQ-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-(7-methyl-1h-indol-3-yl)ethyl]acetamide Chemical compound C=1NC=2C(C)=CC=CC=2C=1CCNC(=O)CC1NC(=O)NC1=O SMLVTOYIPFGBCQ-UHFFFAOYSA-N 0.000 claims 1
- ORLNQODIURCMST-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(1h-pyrrol-2-yl)phenyl]ethyl]acetamide Chemical compound C=1C=C(C=2NC=CC=2)C=CC=1CCNC(=O)CC1NC(=O)NC1=O ORLNQODIURCMST-UHFFFAOYSA-N 0.000 claims 1
- IORHYLHMWHRAJN-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(2-phenylethynyl)piperidin-1-yl]ethyl]acetamide Chemical compound C1CC(C#CC=2C=CC=CC=2)CCN1CCNC(=O)CC1NC(=O)NC1=O IORHYLHMWHRAJN-UHFFFAOYSA-N 0.000 claims 1
- MGEUZXINJTVDBQ-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(3-methoxyphenyl)phenyl]propyl]acetamide Chemical compound COC1=CC=CC(C=2C=CC(=CC=2)C(C)CNC(=O)CC2C(NC(=O)N2)=O)=C1 MGEUZXINJTVDBQ-UHFFFAOYSA-N 0.000 claims 1
- IRVYYFVEWOBGFA-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(3-methylphenyl)phenyl]ethyl]acetamide Chemical compound CC1=CC=CC(C=2C=CC(CCNC(=O)CC3C(NC(=O)N3)=O)=CC=2)=C1 IRVYYFVEWOBGFA-UHFFFAOYSA-N 0.000 claims 1
- KVCRCZGTISUDIT-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(3-nitrophenyl)phenyl]ethyl]acetamide Chemical compound [O-][N+](=O)C1=CC=CC(C=2C=CC(CCNC(=O)CC3C(NC(=O)N3)=O)=CC=2)=C1 KVCRCZGTISUDIT-UHFFFAOYSA-N 0.000 claims 1
- WIIYYNKCHBOAGO-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(4-fluoro-3-methylphenyl)phenyl]propyl]acetamide Chemical compound C=1C=C(C=2C=C(C)C(F)=CC=2)C=CC=1C(C)CNC(=O)CC1NC(=O)NC1=O WIIYYNKCHBOAGO-UHFFFAOYSA-N 0.000 claims 1
- OXWVNWUEMYSZLQ-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(4-fluorophenoxy)phenyl]ethyl]acetamide Chemical compound C1=CC(F)=CC=C1OC(C=C1)=CC=C1CCNC(=O)CC1C(=O)NC(=O)N1 OXWVNWUEMYSZLQ-UHFFFAOYSA-N 0.000 claims 1
- JRSVKPOMJWSJBK-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(4-fluorophenyl)phenyl]propyl]acetamide Chemical compound C=1C=C(C=2C=CC(F)=CC=2)C=CC=1C(C)CNC(=O)CC1NC(=O)NC1=O JRSVKPOMJWSJBK-UHFFFAOYSA-N 0.000 claims 1
- KXFQGBOGUBMENC-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(4-methoxy-3-methylphenyl)phenyl]propyl]acetamide Chemical compound C1=C(C)C(OC)=CC=C1C1=CC=C(C(C)CNC(=O)CC2C(NC(=O)N2)=O)C=C1 KXFQGBOGUBMENC-UHFFFAOYSA-N 0.000 claims 1
- RDWBJHVPHZKYLU-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(4-methoxyphenoxy)phenyl]ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1OC(C=C1)=CC=C1CCNC(=O)CC1C(=O)NC(=O)N1 RDWBJHVPHZKYLU-UHFFFAOYSA-N 0.000 claims 1
- MTUIFOCICNLFLI-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(4-methylphenoxy)phenyl]ethyl]acetamide Chemical compound C1=CC(C)=CC=C1OC(C=C1)=CC=C1CCNC(=O)CC1C(=O)NC(=O)N1 MTUIFOCICNLFLI-UHFFFAOYSA-N 0.000 claims 1
- PSZPBPVFGJHBTF-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(4-methylphenyl)phenyl]ethyl]acetamide Chemical compound C1=CC(C)=CC=C1C(C=C1)=CC=C1CCNC(=O)CC1C(=O)NC(=O)N1 PSZPBPVFGJHBTF-UHFFFAOYSA-N 0.000 claims 1
- FUYYGFOXCHVBJB-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(4-methylsulfanylphenyl)phenyl]ethyl]acetamide Chemical compound C1=CC(SC)=CC=C1C(C=C1)=CC=C1CCNC(=O)CC1C(=O)NC(=O)N1 FUYYGFOXCHVBJB-UHFFFAOYSA-N 0.000 claims 1
- CVEBRFZXTQTDNG-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(4-phenylmethoxyphenyl)phenyl]ethyl]acetamide Chemical compound C=1C=C(C=2C=CC(OCC=3C=CC=CC=3)=CC=2)C=CC=1CCNC(=O)CC1NC(=O)NC1=O CVEBRFZXTQTDNG-UHFFFAOYSA-N 0.000 claims 1
- HZLZBUQEICMDEU-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(6-methoxypyridin-3-yl)phenyl]propyl]acetamide Chemical compound C1=NC(OC)=CC=C1C1=CC=C(C(C)CNC(=O)CC2C(NC(=O)N2)=O)C=C1 HZLZBUQEICMDEU-UHFFFAOYSA-N 0.000 claims 1
- ZCBKHMMOOUJAGQ-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(furan-2-yl)phenyl]ethyl]acetamide Chemical compound C=1C=C(C=2OC=CC=2)C=CC=1CCNC(=O)CC1NC(=O)NC1=O ZCBKHMMOOUJAGQ-UHFFFAOYSA-N 0.000 claims 1
- JHLAWIIVQSFOJU-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(furan-3-yl)phenyl]ethyl]acetamide Chemical compound C=1C=C(C2=COC=C2)C=CC=1CCNC(=O)CC1NC(=O)NC1=O JHLAWIIVQSFOJU-UHFFFAOYSA-N 0.000 claims 1
- QENKBOWWIVNWES-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-[3-(trifluoromethoxy)phenyl]phenyl]propyl]acetamide Chemical compound C=1C=C(C=2C=C(OC(F)(F)F)C=CC=2)C=CC=1C(C)CNC(=O)CC1NC(=O)NC1=O QENKBOWWIVNWES-UHFFFAOYSA-N 0.000 claims 1
- SWLWTRVVOCSUJR-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-[4-(trifluoromethoxy)phenoxy]phenyl]ethyl]acetamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1OC(C=C1)=CC=C1CCNC(=O)CC1C(=O)NC(=O)N1 SWLWTRVVOCSUJR-UHFFFAOYSA-N 0.000 claims 1
- OILZRECTMVSBKC-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-[4-[4-(trifluoromethyl)phenoxy]phenyl]ethyl]acetamide Chemical compound C1=CC(C(F)(F)F)=CC=C1OC(C=C1)=CC=C1CCNC(=O)CC1C(=O)NC(=O)N1 OILZRECTMVSBKC-UHFFFAOYSA-N 0.000 claims 1
- OWVIXEHHOYQWCM-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-hydroxy-2-(4-phenylphenyl)ethyl]acetamide Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1C(O)CNC(=O)CC1NC(=O)NC1=O OWVIXEHHOYQWCM-UHFFFAOYSA-N 0.000 claims 1
- QIBNWYVDFQPFTQ-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[2-methoxy-2-(4-phenylphenyl)ethyl]acetamide Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1C(OC)CNC(=O)CC1NC(=O)NC1=O QIBNWYVDFQPFTQ-UHFFFAOYSA-N 0.000 claims 1
- WDYDOOWPHUJPMH-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[5-(3-methylsulfanylphenyl)-2,3-dihydro-1h-inden-2-yl]acetamide Chemical compound CSC1=CC=CC(C=2C=C3CC(CC3=CC=2)NC(=O)CC2C(NC(=O)N2)=O)=C1 WDYDOOWPHUJPMH-UHFFFAOYSA-N 0.000 claims 1
- OAOVFHJGNLNRAT-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[5-(4-fluoro-3-methylphenyl)-2,3-dihydro-1h-inden-2-yl]acetamide Chemical compound C1=C(F)C(C)=CC(C=2C=C3CC(CC3=CC=2)NC(=O)CC2C(NC(=O)N2)=O)=C1 OAOVFHJGNLNRAT-UHFFFAOYSA-N 0.000 claims 1
- IGORJAVGSRYIIR-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[5-(4-methoxy-3-methylphenyl)-2,3-dihydro-1h-inden-2-yl]acetamide Chemical compound C1=C(C)C(OC)=CC=C1C1=CC=C(CC(C2)NC(=O)CC3C(NC(=O)N3)=O)C2=C1 IGORJAVGSRYIIR-UHFFFAOYSA-N 0.000 claims 1
- ZCNFEPSOJYXFBT-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-[5-(6-methoxypyridin-3-yl)-2,3-dihydro-1h-inden-2-yl]acetamide Chemical compound C1=NC(OC)=CC=C1C1=CC=C(CC(C2)NC(=O)CC3C(NC(=O)N3)=O)C2=C1 ZCNFEPSOJYXFBT-UHFFFAOYSA-N 0.000 claims 1
- NJMHVZCQFIPWHL-UHFFFAOYSA-N 2-(2,5-dioxoimidazolidin-4-yl)-n-methyl-n-[2-(4-phenylphenyl)ethyl]acetamide Chemical compound N1C(=O)NC(=O)C1CC(=O)N(C)CCC(C=C1)=CC=C1C1=CC=CC=C1 NJMHVZCQFIPWHL-UHFFFAOYSA-N 0.000 claims 1
- RRUZCFPTZBMPPW-UHFFFAOYSA-N 2-(4-methyl-2,5-dioxoimidazolidin-4-yl)-n-[2-(4-quinolin-3-ylphenyl)propyl]acetamide Chemical compound C=1C=C(C=2C=C3C=CC=CC3=NC=2)C=CC=1C(C)CNC(=O)CC1(C)NC(=O)NC1=O RRUZCFPTZBMPPW-UHFFFAOYSA-N 0.000 claims 1
- MBGWVEWLFGSZED-UHFFFAOYSA-N 2-(4-methyl-2,5-dioxoimidazolidin-4-yl)-n-[2-[4-(3-methylsulfanylphenyl)phenyl]propyl]acetamide Chemical compound CSC1=CC=CC(C=2C=CC(=CC=2)C(C)CNC(=O)CC2(C)C(NC(=O)N2)=O)=C1 MBGWVEWLFGSZED-UHFFFAOYSA-N 0.000 claims 1
- XOWIGLBFFHBXIC-UHFFFAOYSA-N 2-(4-methyl-2,5-dioxoimidazolidin-4-yl)-n-[2-[4-[3-(trifluoromethoxy)phenyl]phenyl]propyl]acetamide Chemical compound C=1C=C(C=2C=C(OC(F)(F)F)C=CC=2)C=CC=1C(C)CNC(=O)CC1(C)NC(=O)NC1=O XOWIGLBFFHBXIC-UHFFFAOYSA-N 0.000 claims 1
- KWTOJUZBGBMKGK-UHFFFAOYSA-N 2-(4-methyl-2,5-dioxoimidazolidin-4-yl)-n-[5-[3-(trifluoromethoxy)phenyl]-2,3-dihydro-1h-inden-2-yl]acetamide Chemical compound C1C2=CC=C(C=3C=C(OC(F)(F)F)C=CC=3)C=C2CC1NC(=O)CC1(C)NC(=O)NC1=O KWTOJUZBGBMKGK-UHFFFAOYSA-N 0.000 claims 1
- JGSIAOZAXBWRFO-UHFFFAOYSA-N 3-methylsulfanyl-1-phenyl-4,5-dihydrobenzo[g]indazole Chemical compound C1CC2=CC=CC=C2C2=C1C(SC)=NN2C1=CC=CC=C1 JGSIAOZAXBWRFO-UHFFFAOYSA-N 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
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- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
- C07D233/78—Radicals substituted by oxygen atoms
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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| CN104030930A (zh) * | 2014-06-20 | 2014-09-10 | 河北序能生物技术有限公司 | 一种反式-（1r,2s）-2-（3,4-二氟苯基）环丙胺盐酸盐的合成方法 |
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| US6979750B1 (en) | 2003-04-18 | 2005-12-27 | The Regents Of The University Of California | Thyronamine derivatives and analogs and methods of use thereof |
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| CN101528711A (zh) | 2006-08-31 | 2009-09-09 | 先灵公司 | 可用作抗细菌剂的乙内酰脲衍生物 |
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| CN101024619B (zh) * | 2007-03-29 | 2010-12-01 | 上海大学 | N-取代邻溴苄酰胺的合成方法 |
| US8470841B2 (en) | 2008-07-09 | 2013-06-25 | Sanofi | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
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| BR112012006572A2 (pt) | 2009-09-25 | 2016-04-26 | Oryzon Genomics Sa | inibidores de demetilase-1 de lisina específicos e seu uso |
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| WO2011106105A2 (en) | 2010-02-24 | 2011-09-01 | Oryzon Genomics, S.A. | Inhibitors for antiviral use |
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| SMT201800323T1 (it) | 2010-07-29 | 2018-07-17 | Oryzon Genomics Sa | Inibitori di demetilasi lsd1 a base di arilciclopropilammina e loro uso medico |
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| EP2712315B1 (en) | 2011-02-08 | 2021-11-24 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for myeloproliferative disorders |
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| US20140296255A1 (en) * | 2011-05-19 | 2014-10-02 | Oryzong Genomics, S.A. | Lysine demethylase inhibitors for thrombosis and cardiovascular diseases |
| PE20141692A1 (es) | 2011-10-20 | 2014-11-08 | Oryzon Genomics Sa | Compuestos de (hetero) aril ciclopropilamina como inhibidores de lsd1 |
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| WO2014051538A1 (en) * | 2012-09-25 | 2014-04-03 | Empire Technology Development Llc | Oxidizing agents on pigments |
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| CN103588758A (zh) * | 2013-11-04 | 2014-02-19 | 南京大学 | 一类含1,4-苯并二噁烷骨架的硝基咪唑衍生物的合成、制备及其在抗癌药物中的应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104030930A (zh) * | 2014-06-20 | 2014-09-10 | 河北序能生物技术有限公司 | 一种反式-（1r,2s）-2-（3,4-二氟苯基）环丙胺盐酸盐的合成方法 |
| CN104030930B (zh) * | 2014-06-20 | 2016-02-24 | 河北序能生物技术有限公司 | 一种反式-（1r,2s）-2-（3,4-二氟苯基）环丙胺盐酸盐的合成方法 |
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